Procedures for determining the presence or absence of specific organisms or viruses in a test sample commonly rely upon nucleic acid-based probe testing. To increase the sensitivity of these tests, an amplification step is often included to increase the number of potential nucleic acid target sequences present in the test sample. There are many procedures for amplifying nucleic acids which are well known in the art, including, but not limited to, the polymerase chain reaction (PCR), (see, e.g., Mullis, “Process for Amplifying, Detecting, and/or Cloning Nucleic Acid Sequences,” U.S. Pat. No. 4,683,195), transcription-mediated amplification (TMA), (see, e.g., Kacian et al., “Nucleic Acid Sequence Amplification Methods,” U.S. Pat. No. 5,399,491), ligase chain reaction (LCR), (see, e.g., Birkenmeyer, “Amplification of Target Nucleic Acids Using Gap Filling Ligase Chain Reaction,” U.S. Pat. No. 5,427,930), strand displacement amplification (SDA), (see, e.g., Walker, “Strand Displacement Amplification,” U.S. Pat. No. 5,455,166), and loop-mediated isothermal amplification (see, e.g., Notomi et al., “Process for Synthesizing Nucleic Acid,” U.S. Pat. No. 6,410,278). A review of several amplification procedures currently in use, including PCR and TMA, is provided in HELEN H. LEE ET AL., NUCLEIC ACID AMPLIFICATION TECHNOLOGIES (1997).
A concern with amplification is the possibility of cross-contamination, since transferring even a minute amount of target-containing sample to a target-negative sample could lead to the production of billions of target sequences in the “negative” sample. As a consequence, a test may indicate a positive result for a sample actually lacking nucleic acid from an organism or virus of interest. The source of a contaminating sample transfer may be an aerosol or bubbles released from a sample tube when a cap component of the sample tube is removed or penetrated by a practitioner or instrument. To minimize such sources of contamination, penetrable caps having filtering means were recently introduced and are disclosed by Anderson et al., “Collection Device and Method for Removing a Fluid Substance from the Same,” U.S. Patent Application Publication No. US 2001-0041336 A1, and Kacian et al., “Penetrable Cap,” U.S. Patent Application Publication No. US 2002-0127147 A1.
Components of penetrable caps generally exert a retention force against fluid transfer devices (e.g., pipette tips) as they are being withdrawn from corresponding sample tubes. See, e.g., Ammann et al., “Automated Process for Isolating and Amplifying a Target Nucleic Acid Sequence,” U.S. Pat. No. 6,335,166 (an instrument for performing amplification assays on test samples which includes a robotic pipettor for obtaining test sample from a sample tube is disclosed). The retention force may be attributable to, for example, the sealing material of the cap and/or filtering means included within the cap. If the retention force is too great, a sample tube may be drawn out a sample carrier holding the sample tube by an exiting pipettor. In a more extreme case, the retention force of the cap and the sample tube holding force of the sample carrier are each great enough that the sample carrier is lifted vertically as the fluid transfer device is being withdrawn from the sample tube.
Conventional sample carriers commonly rely upon springs to immobilize distal ends of sample tubes, biasing the sample tubes against one or more opposing surfaces of the sample carriers. And more recently, a sample carrier has been described which further includes a top wall portion having a plurality of openings which are configured and arranged so that penetrable caps affixed to the vessel components of sample tubes are positioned snugly within the openings when the sample tubes are held by the sample carrier, thereby centering the sample tubes by restricting lateral movement of the corresponding caps within the openings. See Dale et al., “Sample Carrier and Drip Shield for Use Therewith,” U.S. Patent Application Publication No. US 2003-0017084 A1. What these sample carriers lack, however, is a mechanism for ensuring that sample tubes remain in the sample carriers during automated sampling procedures when the retention force of a cap is greater than the holding force of the sample carrier on an associated vessel component. As a consequence, there is a risk that penetrable caps which exert too great a retention force against fluid transfer devices will be withdrawn, along with their associated vessel components, from sample carriers during automated sampling procedures. Thus, a need exists for a sample carrier capable of containing sample tubes having penetrable caps in their allotted positions on the sample carrier during automated sampling procedures.